Clinical trials evaluating a variety of agents in the management of patients with adult T cell leukemia have continued. These trials include evaluations of agents that target CD2 (siplizumab), CD25 (daclizumab) and CD52 (alemtuzumab). The phase I trial of siplizumab has completed accrual to its initially planned evaluation of a two or three day course of treatment administered on an every other week basis for up to 16 weeks. Seven cohorts of patients were treated with doses ranging from 0.4 to 4.8 mg/kg. There were no dose-limiting toxicities and T cell depletion was observed as expected. Down modulation of the siplizumab target, CD2, was observed within 24 hours of antibody administration in the peripheral blood and appeared to impair the activity of the administered antibody from producing further decreases in peripheral blood T cell numbers particularly in patients with high white blood cell counts. Three additional cohorts of patients are being treated with doses ranging from 0.8 to 4.8 mg/kg administered as a single infusion weekly. The 0.8 mg/kg dose level has completed accrual with no dose-limiting toxicity and accrual to the final two cohorts continues. Partial and complete responses have been observed with the longest duration of response being 18 months and ongoing. The phase II trial of daclizumab has shown that the agent is inactive in patients with the lymphomatous or acute leukemic form of adult T cell leukemia but is active in patients with the smoldering and chronic forms of the disease. It is thought that these earlier forms remain dependent on IL2 signaling and that the responses are due to apoptosis due to cytokine deprivation. Our phase II trial of alemtuzumab continues to accrue patients as responses were observed in patients during the first stage of the trial. Accrual to a total of 29 patients is planned. Responses have been observed in patients with acute leukemia but not in the lymphomatous form of the disease. A phase I clinical trial of humanized MiK-beta-1, directed at the beta chain of the IL-2 receptor continues accrual in patients with large granular lymphocyte leukemia. No dose-limiting toxicity has been observed and the highest dose level planned for the study will begin accrual. Reduction if the numbers of peripheral blood malignant cells has been observed. In addition a phase I trial of HeFi-1, a murine monoclonal antibody directed at CD30 has almost completed accrual with only a single patient left to accrue.